J. Org.
5444
Chem. 1985, 50, 5444-5446
Attempts to extend this process to sulfides bearing alkyl substitution at the allylic terminus have been unsuccessful. For example, if l-(phenylthio)-3-methyl-2-butene(the allylically transposed isomer of 5) is reacted with substrate 19, then no products from direct SH2'reaction are found: only 17 and the reduction product from 19 are isolable, albeit in poor yield.15 (Note eq 5).
Scheme I
bMe ""Cf
8'. 1"
1"-' (21%)
~
(16 %I
5'". * 4
Although the yields of this process are not as high as for allylation using allyltri-n-butylstannane, the success of this rather complex chain process despite numerous a priori reasonable side reactions is noteworthy, as is the separation of chain-carrying steps16in the mechanism. The results described herein demonstrate that the design of complex free radical chains for use in organic synthesis is feasible, and further investigations along such lines are in progress in our laboratories.
Acknowledgment. We thank the National Science Foundation for generous support of this research. Registry No. 5, 34043-60-2; 6, 701-75-7; 7, 540-51-2; 8, 42272-94-6; cis-9, 928-91-6; trans-9, 928-92-7; 10, 627-18-9; 11, 13175-35-4;cis-l2,50273-95-5; tram-12,25143-94-6; 13,574-98-1; 14, 99097-66-2; cis-15, 99097-67-3; trans-15, 99097-68-4; 16, 53560-49-9; 17,99097-69-5;ck-18,99097-70-8; tram-18,99097-71-9; 19,83160-36-5;20,83160-38-7;21,19914-92-2;22,99097-72-0;23, 99097-73-1; 24, 71404-67-6; hexabutylditin, 813-19-4. (15) (a) The production of 17 may be rationalized by allylic rearrangement of l-(phenylthio)-3-methyl-2-butene to give 5, followed by reaction of 5 with a carbon-centered radical generated from 19. For leading references on the rearrangement of allylic sulfides, note: Kozikowski, A. P.; Huie, E.; Springer, J. P. J.Am. Chem. SOC. 1982,104,2059 and references therein. (b) Similar results were obtained for reaction of 19 with l-(phenylthio)-2-butene (the allylically transposed isomer of 6). In this case, 42% of the reduced product was obtained, along with 7% of 18 and 7% of the product of direct SH2' substitution. (16) In free radical allylation using allylstannanes, C-C bond formation and generation of substrate radicals are inevitably linked to one another, since chain-carrying stannyl radicals are generated directly from the C-C bond forming event. In the present process, C-C bond formation and generation of chain-carrying stannyl radicals occur as separate and discrete steps in the chain.
Gary E. Keck,* Jeffrey H. Byers D e p a r t m e n t of C h e m i s t r y U n i v e r s i t y of Utah Salt L a k e C i t y , Utah 84112 Received J u n e 10, 1985
Resolution of Ketones via Chiral Acetals. Kinetic Approach S u m m a r y : When a chiral acetal is treated with triisobutylaluminum a t low temperature, one diastereoisomer reacts much faster than the other and the resulting enol ether is transformed to optically pure ketone.
Sir: In contrast to the generation of optically active carbonyl compounds by asymmetric alkylation, which is now used with great frequency in synthesis and for which many
bMe selective reagents are known,' methods for the efficient resolution of carbonyl compounds are still quite limited. Classical approaches to the optical activation of ketones are not always reliable.2,3 This communication reports the successful development of a new type of resolution for ketones based on a kinetic approach. We have recently described the nucleophilic cleavage of chiral acetals derived from (-)-(2R,4R)-2,4-pentanediol using organometallic reagentsS4 By studying this reaction in detail, it was discovered that an enol ether was formed under certain reaction conditions. Thus, treatment of acetal 1 with triisobutylaluminum (TIBA) in dichloro-
5 1
i-Bu,Al CHICI, ( 5 eq)
*
bUH
98 %
O°C ; 30 m 2
Y
methane at 0 "C for 30 min produced the enol ether 2 in (1) For reviews, see: "Asymmetric Synthesis", Vol. 2 and 3, Morrison, J. D., Ed.; Academic Press: New York, 1983 and 1984. (2) For reviews, see: Wilen, S. H. In "Topics in Stereochemistry"; Eliel, E. L., Allinger, N. L., Eds.; Wiley-Interscience: New York, 1971; Vol6, p 107. See also: Newman, P. "Optical Resolution Procedures for Chemical Compounds"; Optical Resolution Information Center: Manhattan College, New York, 1984; Vol 3, p 479. (3) Recently Johnson reported an elegant resolution technique of ketone based on the addition of an optically pure sulfoximine: Johnson, C. R.; Zeller, J. R. J. Am. Chem. SOC.1982,104,4021; Tetrahedron 1984, 40, 1225. (4) (a) Mori, A.; Fujiwara, J.; Maruoka, K.; Yamamoto, H. J. Organomet. Chem. 1985,285,83. Mori, A.; Fujiwara, J.; Maruoka, K.; Yamamoto, H. Tetrahedron Lett. 1983, 24, 4581. Mori, A.; Maruoka, K.; Yamamoto,H. Ibid. 1984,25,4421. See also: (b)Bartlett, P. A.; Johnson, W. S.; Elliott, J. D. J.Am. Chem. SOC.1983, 105, 2088. (c) Johnson, W. S.;Elliott, R.; Elliott, J. D. Ibid. 1983, 105, 2904. (d) Elliott, J. D.; Choi, V. M. F.; Johnson, W. S. J. Org. Chem. 1983,48, 2294. (e) Choi, V. M. F.; Elliott, J. D.; Johnson, W. S. Tetrahedron Lett. 1984, 25, 591. (f) Ghribi, A.; Alexakis, A,; Normant, J. F. Ibid. 1984,25,3083. (9) Lindell, S. D.; Elliott, J. D.; Johnson, W. S. Ibid. 1984,25,3947. (h) Johnson, W. S.; Crackett, P. H.; Elliott, J. D.; Jagodzinski, J. J.; Lindell, S. D.; Natarajan, S. Ibid. 1984,25,3951. (i) Johnson, W. S.; Edington, C.; Elliott, J. D.; Silverman, I. R. J. Am. Chem. SOC.1984, 106, 7588.
0022-3263/85/1950-5444$01.50/00 1985 American Chemical Society
J. Org. Chem., Vol. 50,No. 25,
Communications
1985 5445
Table I. Resolution of Ketones Using Chiral Acetalsa
entry
1 2 3
4 5 6
7 8
acetalb
b (5-
h
9
11
aluminum reagent (equiv)
enol ether yield (%Ac (ratio)
reactn condn 'C, h
recovered acetal yield (%)' (ratio) e
TIBA (2) TIBA (2) DIBAH (2)
0, 3 -20,5 -20,3
TIBA (4) TIBA (2)
-20,2 -20,l
TIBA (4)
-20,3
25 (99% diastereochemicallypure by GC analysis). Mild hydrolysis of 4 (0.1 N HC1-acetone, 0 "C, 1.5 h) produced (R)-2methylcyclohexanone [.]24D -15.9" (neat)? with an enantiomeric excess of > 9 ~ 5 % . When ~ the reaction was carried out to about 70% completion (0 O C , 3 h), the recovered acetal was separated chromatographically and shown to (5) It should be noted that the effective elimination of the acetal was only observed with the acetal from 2,4-pentanediol. Thus, treatment of the ethylene acetal of cyclohexanone with excess TIBA at 25 "C for 24 h gave the reduced cleavage product (CH2)5CHO(CH2)20H in 38% yield. (6) (-)-(2R,4R)-2,4-Pentanediol was purchased from Wako Pure Chemical Industries Ltd. and recrystallized from ether: Ito,K.; Harada, Jpn. 1980,53, 3367. T.; Tai,A. Bull. Chem. SOC. (7) GC analysis (25-m PEG-HT capillary column) of this product revealed a mixture of two diastereoisomers of the ratio of ca. 3:7. (8) Lit. [aI2OD-16.6" (neat): Enders, D. Chemtech 1981,504. Enders, D.; Eichenauer, H. Chem. Ber. 1979,112, 2933. (9) Optical purity was determined by conversion to cis-2-methylcyclohexanol (L-Selectride (Aldrich) at -78 "C) and GC analysis of its (+)-methoxy-a-(trifluoromethy1)phenylaceticacid (MTPA) ester.
Scheme I1 D I BAH
DIBAH
""Tf o@Me* 42
5
X
be >99% pure by GC analysis. From this acetal (S)-2methylcyclohexanone was prepared in 78% yield: [(uIz4D +14.9' (neat).8p10 The stereochemical outcome of the reaction of diisobutylaluminum hydride (DIBAH) with diastereomers 3 is illustrated in Scheme 11. Here, the recovered acetal 3 (42%) was diastereomerically pure (>99%) and the re(10)Optical purity was >95%ee by the method of ref 9.
5446
J. Org. Chem. 1985,50, 5446-5448
*Scheme I11
0
"
91%
"
"
~
&RP
s
186%
7
duced ether 5 (49%) was obtained in 90% diastereomeric purity by GC analysis.11J2 Furthermore, pure 5 was readily prepared by terminating the reaction a t 30% completion (-20 'C, 3 h). Oxidation followed by basic treatment4 of 5 gave (+)-(1S,2R)-2-methylcyclohexanol (6),l3 [(YIz4D +20.3' (c 3.21, ethanol),14in 74% yield with >99% de and 98% ee.15 The generality of the reaction is apparent from the results summarized in Table I. The efficiency of our new method is highlighted by a rapid and convenient synthesis of (-)-(5')-5-hexadecanolide (7), pheromone of Vespa orientalis.16 The sequence of the reactions utilized is outlined in Scheme 111. Acetalization of the readily available ketone 8l' with (-)(2R,4R)-2,4-pentanediolgave diastereomers 9. Treatment of 9 with 1.5 equiv of DIBAH at 0 'C for 30 min gave, after chromatographic purification, optically pure acetal (2R,4R,7S)-9in 37% yield with 97% de. Mild hydrolysis in 0.1 N HC1-acetone furnished pure (S)-8in 86% yield: [a]24D +81.0° (c 1.04, ether). Baeyer-Villiger oxidation of (S)-8with m-chloroperbenzoic acid in chloroform a t 25 'C for 24 h yielded the lactone 718 in 75% yield: [(r]%D -38.3' (c 1.17, THF).lGe As implied above, the process is remarkably general and should in many cases provide a practical, if not unique, route to optically pure ketones. Another noteworthy aspect of this approach to chiral material is that the enol ether itself may provide a point of departure for further transformations. Registry No. 1, 5422-00-4; 2, 99299-19-1; 3 (isomer l), 99299-20-4; 3 (isomer 2), 99341-26-1; 4, 99299-21-5; 5 (isomer l), 99299-22-6; 5 (isomer 2), 99341-27-2; 5 (isomer 3), 99341-28-3; 6, 15963-35-6; 7, 59812-97-4; 8, 99299-27-1; (S)-8, 99341-36-3; 9 (isomer l),99299-28-2; 9 (isomer 2), 99341-35-2; (CH2),&HO(CH,),OH, 1817-88-5; (i)-2-methylcyclohexanone,24965-84-2; (-)-(2R,4R)-2,4-pentanediol, 42075-32-1; 2-allylcyclohexanone acetal (isomer l),99299-23-7; 2-allylcyclohexanoneacetal (isomer 2), 99341-29-4; 2-allylcyclohexanone enol ether, 99299-24-8; 2cyclohexylcyclohexanone acetal (isomer l),99299-25-9; 2-cyclohexylcyclohexanone acetal (isomer 2), 99341-30-7; 3-methyl-
cyclohexanone acetal (isomer l), 96249-24-0; S-methylcyclohexanone acetal (isomer 2), 99341-31-8; 3,3,5-trimethylcyclohexanone acetal (isomer l),99341-32-9; 3,3,5-trimethylcyclohexanone acetal (isomer 2), 99341-33-0; 2-methylcycloheptanone acetal (isomer l),99299-26-0; 2-methylcycloheptanone acetal (isomer 2), 99341-34-1; 2-propylcyclohexanone acetal (isomer l), 99299-29-3;bicyclo[3.3.O]octan-2-one acetal (isomer l),99299-30-6; bicyclo[3.3.0]octan-2-oneacetal (isomer 2), 99341-37-4; cyclohexanone ethylene acetal, 177-10-6; (R)-2-methylcyclohexanone, 22554-29-6; (S)-2-methylcyclohexanone,22554-27-4; cyclohexanone, 108-94-1; 2-allylcyclohexanone, 94-66-6; 2-cyclohexylcyclohexanone, 90-42-6; 3-methylcyclohexanone, 591-24-2; 3,3,5-trimethylcyclohexanone,873-94-9; 2-methylcycloheptanone, 32405-37-1. 932-56-9; cis-bicyclo[3.3.0]octan-2-one,
Supplementary Material Available: Experimental Section (7 pages). Ordering information is given on any current masthead page. Atsunori Mori, Hisashi Yamamoto* Department of Applied Chemistry Nagoya University, Chikusa Nagoya 464, Japan Received August 6, 1985
Diisopinocampheylchloroborane, a Remarkably Efficient Chiral Reducing Agent for Aromatic Prochiral Ketones
Summary: Diisopinocampheylchloroborane, readily prepared in high chemical and optical purities (99% ee) from (+)-a-pinene (92% ee) via hydroboration, followed by treatment with dry hydrogen chloride in ether, reduces ketones at convenient rates at -25 O C . The chiral induction is excellent for the reduction of aromatic prochiral ketones. Sir: Optically active secondary alcohols are important starting materials for chiral syntheses.l Their synthesis by the reduction of prochiral ketones with chiral reducing agents has been actively pursued in recent years by organic chemists. Many interesting reagents have been developed, some of them achieving remarkable success.2 For example, Noyori's Bind-H reduces several classes of prochiral ketones with high chiral i n d ~ c t i o n . ~ Trialkylboranes and borohydrides have also been applied as chiral reducing agent^.^ Of these, the Midland reagent, B-3-pinanyl-9-borabicyclo[ 3.3.llnonane (1) (Aldrich, R-Alpine-Borane) prepared from (+)-a-pinenehas
6.D 1
I
(11)lR,2R:lR,2S:lS,2R:lS,2S= 0.7:3.0:89.66.7by GC analysis. (12)The recovered acetal was further reduced with excess DIBAH (5 equiv) at 25 "C for 6 h to give the cleavage product in 83% yield with low diastereoselectivity: lR,2R:lR,2S:lS,2R:lS,ZS= 064036. (13)The cis:trans ratio was >991 by GC analysis. (14)Lit. [ a I z 5+15.7" ~ (c 3.4,EtOH): Jones, J. R.; Takemura, T. Can. J. Chem. 1982,60,2950. (15)Optical purity was determined by GC analysis of the (+)-MTPA ester. (16)(a) Ikan, R.; Gottlieb, R.; Bergmann, E. D; Ishay, J. J. Insect Physiol. 1969,15,1709.For the synthesis of 7 (b) Coke, J. L.; Richon, A. B. J. Org. Chem. 1976,41,3516. (c) Pirkle, W.H.; Adams, P. E. Ibid. 1979, 44,2169. SolladiB, G.; Moghadam, F. M. Ibid. 1982,47,91. (e) Servi, S. Tetrahedron Lett. 1983,24, 2023. (f) Fujisawa, T.; Itoh, T. Nakai, M.; Sato, T. Ibid. 1986,26,771. (17)HHjek, M.; Milek, J. Collect. Czech. Chem. Commun. 1976,41, 746. (18)Identical in all respects with the reported data.16
emerged as a very useful chiral reducing agent.5 Midland and his co-workers initially reported that 1 reduces 1deuterioaldehydes and a,p-acetylinic ketones in tetrahydrofuran (THF) at room temperature with excellent (1)For a recent application, see: Rosen, T.; Heathcock, C. H. J. Am. Chem. SOC. 1986,107,3731. (2)"Asymmetric Synthesis", Vol. 2;Morrison, J. D.,Ed., Academic Press: New York, 1983;Chapters 2,3, and 4. (3)Noyori, R.; Tomino, I,;Tanimoto, Y.; Nishizawa, M. J. Am. Chem. SOC. 1984,106,6709, 6717. (4)Reference 3,Chapter 2. (5)(a) Midland, M. M.; Tramontano, A.; Zderic, S. A. J . Organomet. Chem. 1978,156,203.(b) The other isomer, S-Alpine-Borane,is obtained from (-)-a-pinene.
0022-3263/85/1950-5446$01.50/00 1985 American Chemical Society
